Neulasta

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Neulasta

WARNINGS

Included as part of the PRECAUTIONS section.

PRECAUTIONS

Splenic Rupture

Splenic rupture, including fatal cases, can occur following
the administration of Neulasta. Evaluate for an enlarged spleen or splenic
rupture in patients who report left upper abdominal or shoulder pain after
receiving Neulasta.

Serious Allergic Reactions

Serious allergic reactions, including anaphylaxis, can occur
in patients receiving Neulasta. The majority of reported events occurred upon
initial exposure. Allergic reactions, including anaphylaxis, can recur within
days after the discontinuation of initial anti-allergic treatment. Permanently
discontinue Neulasta in patients with serious allergic reactions. Do not
administer Neulasta to patients with a history of serious allergic reactions to
pegfilgrastim or filgrastim.

Potential for Tumor Growth Stimulatory Effects on Malignant
Cells

The granulocyte-colony stimulating factor (G-CSF) receptor
through which pegfilgrastim and filgrastim act has been found on tumor cell
lines. The possibility that pegfilgrastim acts as a growth factor for any tumor
type, including myeloid malignancies and myelodysplasia, diseases for which
pegfilgrastim is not approved, cannot be excluded.

Patient Counseling Information

Advise patients of the following risks:

Splenic rupture

Acute Respiratory Distress Syndrome

Serious allergic reactions

Sickle cell crisis

Have patients immediately contact their healthcare provider
and report:

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

No carcinogenicity or mutagenesis studies have been
performed with pegfilgrastim.

Pegfilgrastim did not affect reproductive performance or
fertility in male or female rats at cumulative weekly doses approximately 6 to
9 times higher than the recommended human dose (based on body surface area).

Reproductive and Developmental Toxicology

Pregnant rabbits were dosed with pegfilgrastim
subcutaneously every other day during the period of organogenesis. At
cumulative doses ranging from the approximate human dose to approximately 4
times the recommended human dose (based on body surface area), treated rabbits
exhibited decreased maternal food consumption, maternal weight loss, as well as
reduced fetal body weights and delayed ossification of the fetal skull;
however, no structural

anomalies were observed in the offspring from either study.
Increased incidences of post-implantation losses and spontaneous abortions
(more than half the pregnancies) were observed at cumulative doses
approximately 4 times the recommended human dose, which were not seen when
pregnant rabbits were exposed to the recommended human dose.

Three studies were conducted in pregnant rats dosed with
pegfilgrastim at cumulative doses up to approximately 10 times the recommended
human dose at the following stages of gestation: during the period of
organogenesis, from mating through the first half of pregnancy, and from the
first trimester through delivery and lactation. No evidence of fetal loss or
structural malformations was observed in any study. Cumulative doses equivalent
to approximately 3 and 10 times the recommended human dose resulted in
transient evidence of wavy ribs in fetuses of treated mothers (detected at the
end of gestation but no longer present in pups evaluated at the end of
lactation).

Use In Specific Populations

Pregnancy

Pregnancy Category C

There are no adequate and well-controlled studies in
pregnant women. Pegfilgrastim was embryotoxic and increased pregnancy loss in
pregnant rabbits that received cumulative doses approximately 4 times the recommended
human dose (based on body surface area). Signs of maternal toxicity occurred at
these doses. Neulasta should be used during pregnancy only if the potential
benefit to the mother justifies the potential risk to the fetus.

In animal reproduction studies, when pregnant rabbits
received pegfilgrastim at cumulative doses approximately 4 times the
recommended human dose (based on body surface area), increased embryolethality
and spontaneous abortions occurred. Signs of maternal toxicity (reductions in
body weight gain/food consumption) and decreased fetal weights occurred at
maternal doses approximately equivalent to the recommended human dose (based on
body surface area). There were no structural anomalies observed in rabbit offspring
at any dose tested. No evidence of reproductive/developmental toxicity occurred
in the offspring of pregnant rats that received cumulative doses of pegfilgrastim
approximately 10 times the recommended human dose (based on body surface area) [see
Nonclinical Toxicology].

Women who become pregnant during Neulasta treatment are
encouraged to enroll in Amgen's Pregnancy Surveillance Program. Patients or
their physicians should call 1-800-77-AMGEN (1-800-772-6436) to enroll.

Nursing Mothers

It is not known whether pegfilgrastim is secreted in human
milk. Other recombinant G-CSF products are poorly secreted in breast milk and
G-CSF is not orally absorbed by neonates. Caution should be exercised when administered
to a nursing woman.

Pediatric Use

Safety and effectiveness of Neulasta in pediatric patients
have not been established. The adverse reaction profile and pharmacokinetics of
pegfilgrastim were studied in 37 pediatric patients with sarcoma. The mean (±
standard deviation [SD]) systemic exposure (AUC0-inf) of pegfilgrastim after
subcutaneous administration at 100 mcg/kg was 22.0 (± 13.1) mcg·hr/mL in the 6
to11 years age group (n = 10), 29.3 (± 23.2) mcg·hr/mL in the 12 to21 years age
group (n = 13), and 47.9 (± 22.5) mcg·hr/mL in the youngest age group (0 to5
years, n = 11). The terminal elimination half-lives of the corresponding age
groups were 20.2 (± 11.3) hours, 21.2 (± 16.0) hours, and 30.1 (± 38.2) hours,
respectively. The most common adverse reaction was bone pain.

Geriatric Use

Of the 932 patients with cancer who received Neulasta in
clinical studies, 139 (15%) were age 65 and over, and 18 (2%) were age 75 and
over. No overall differences in safety or effectiveness were observed between
patients age 65 and older and younger patients.

Renal Impairment

In a study of 30 subjects with varying degrees of renal
dysfunction, including end stage renal disease, renal dysfunction had no effect
on the pharmacokinetics of pegfilgrastim. Therefore, pegfilgrastim dose
adjustment in patients with renal dysfunction is not necessary [Clinical
Pharmacology (12.3)].

Last reviewed on RxList: 6/4/2012
This monograph has been modified to include the generic and brand name in many instances.